Abstract Sleep-disordered breathing (SDB) is characterized by recurrent respiratory events followed by arousal and/or a desaturation. However, only respiratory events with 3-4% desaturation associated with adverse cardiovascular outcome. Whether heart rate changes measured by R-R interval dips (RRDI) during sleep adversely affect the long- term outcome is unknown. Recent data showed that symptomatic volunteers with mild and non-apneic respiratory events, without significant desaturation or arousals, developed significant heart rate changes and increased work of breathing. Furthermore, the administration of continuous positive airway pressure (CPAP) corrected abnormal airway mechanics and associated heart rate changes. Therefore, accounting for these abnormal respiratory events, which do not reach current thresholds for the definition of ?abnormal events? by criteria based on electroencephalogram (EEG) changes or a fall in oxygen saturation, in clinical practice may have significant implications for diagnosis and outcome. The main objective of this proposal is to examine the prospective relationship of respiratory-related heart rate changes during sleep with incident cardiovascular disease (CVD) in a longitudinal community-based cohort. The proposed study has two main objectives. The first (aim 1) is to assess the relationship between respiratory events (with or without desaturations) and RRDI from single lead ECG using Wisconsin sleep cohort database (N=1546). This component will allow the use of RRDI as a surrogate of SDB in any sleep study; therefore it will have broad clinical implications in diagnosing SDB. The second objective (aims 2) is to determine the predictors of long-term incidence of cardiovascular disease using the new definition of respiratory events that includes automated measurements of heart rate responses related to respiratory events during sleep independent of oxyhemoglobin desaturation. There will be two specific aims to address the following hypotheses: (1) That RRDI during sleep is associated with respiratory events index (REI) independent of oxyhemoglobin desaturations. (2) That increased respiratory-related RRDI during sleep is associated with increased incidence of CVD.